Efficacy and safety of methotrexate plus hydroxychloroquine combination therapy vs. methotrexate monotherapy in the treatment of rheumatoid arthritis: A randomized controlled clinical trial

Abstract Objective To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA). Methods Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12‐week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL‐BREF) and the treatment‐emergent adverse events (TEAEs) for all the participants in the study. Results At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed ( p > .05). Conclusion In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first‐line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.